1. Field of the Invention
The present invention relates to methods and materials for the synthesis of organic compounds.
2. Description of Related Art
Methodologies involving the synthesis of organic molecules play an important role in many technical fields. Materials science, agriculture, biology, and medicine, rely on organic compounds produced by synthetic methods for their ongoing successes and future progress. Consequently, in the past century artisans have devoted significant efforts to the development of new methodologies for the synthesis of various organic compounds. The large number of synthetic methodologies known in the art as a result of these endeavors allows artisans to construct molecules of great complexity. As complex organic molecules become more and more important in a number of scientific disciplines, the ability to prepare key synthetic entities in both a practical and economical fashion becomes increasingly more valuable (see, e.g. Wender et al., Acc. Chem. Res. 2008, 41, 40-49).
Of the many synthetic methods used to generate organic compounds, transition metal-catalyzed cross-coupling reactions are known as one of the most effective means of constructing carbon-carbon (C—C) and carbon-heteroatom (C—X such as C—N) bonds (see, e.g. Negishi et al., Acc. Chem. Res. 1982, 15, 340-348; Metal-Catalyzed Cross-Coupling Reactions; Diedrich, F., Meijere, A., Eds.; Wiley-VCH: Weinheim, 2004; Vol. 2.; Hassan et al., Chem. Rev. 2002, 102, 1359-1469; Topics in Current Chemistry; Miyaura, N., Ed.; Vol. 219; Springer-Verlag: New York, 2002; Corbet et al., Rev. 2006, 106, 2651-2710; Negishi, Bull. Chem. Soc. Jpn. 2007, 80, 233-257). Carbon-nitrogen bonds are ubiquitous in medicinal agents and natural products. Transition metal-catalyzed amination reactions, pioneered by Buchwald and Hartwig, are amongst the most powerful methods available for accessing these coveted motifs. Copper- and palladium-mediated aminations of aryl halides and triflates are now well-established and examples of mesylate and tosylate aminations have been reported. Most recent efforts have focused on the amination of classically “inert” phenolic derivatives, i.e., aryl methyl ethers and aryl pivalate esters which could potentially be used in multistep synthesis.
Despite advances in this technology, general methodologies that provide efficient and cost-effective cross-coupling of phenol derivatives have yet to be realized. With the aim of assembling polysubstituted aryl amines, motifs commonly encountered in drug scaffolds, naturally-occurring small molecules, pesticides, ligands for catalysis, and materials chemistry, we worked to discover versatile class of phenol-derived substrates that could undergo transition metal-catalyzed amination.